Temporal lobe epilepsy is a common form of adult epilepsy associated with hippocampal damage (mesial temporal sclerosis). Therefore, understanding the mechanisms mediating protection from neurodegeneration subsequent to seizure activity is an essential part of any attempt at preventing seizure-induced damage. Our preliminary data indicate that neural grafting and sham surgery, performed prior to kainic acid (KA) administration in rats, provide neuroprotection from seizure-induced damage, without apparent changes in seizure susceptibility. The goal of this proposal is to identify the mechanism by which neuroprotection occurs in grafted/sham animals. Given that both grafted and sham operated animals appear to show similar levels of neuroprotection, we will first investigate the role of a factor which is common to both procedures: incidental damage to input pathways to the hippocampus, in particular the fimbria-fornix. We will also examine whether hippocampal grafts produce spontaneous recurrent seizures which would, in turn, provide protection from the degenerative effects of a more severe seizure and, whether pharmacological prevention of spontaneous seizures will reduce the protective effect of the graft. Finally, we will determine whether the neuroprotection conferred is a permanent condition, indicating morphological changes in the brain, or whether it disappears over time. Understanding the mechanisms by which neuroprotection occurs in grafted animals, may allow us to develop new approaches in the prevention or treatment of seizure-induced brain damage.